bims-mesote Biomed News
on Mesothelioma
Issue of 2022–12–25
twelve papers selected by
Laura Mannarino, Humanitas Research
  1. Diagnostic and Therapeutic Challenges of Malignant Pleural Mesothelioma.
  2. AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma.
  3. Clinical, Laboratory, Histological, Radiological, and Metabolic Features and Prognosis of Malignant Pleural Mesothelioma.
  4. Considerations for Imaging of Malignant Pleural Mesothelioma: A Consensus Statement from the International Mesothelioma Interest Group (iMig).
  5. New Insights in Pleural Mesothelioma Classification Update: Diagnostic Traps and Prognostic Implications.
  6. The clinical utility of the LENT score in patients with malignant pleural mesothelioma.
  7. Quantitative Assessment of Asbestos Fibers in Normal and Pathological Peritoneal Tissue-A Scoping Review.
  8. Presurgical radiation and chemotherapy in preparation for thoracic tumor resection.
  9. BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms.
  10. A Case Report of Mesothelioma Response to Endocrine Therapy in Synchronous Breast Cancer and Pleural Epithelioid Mesothelioma: A Double Exemestane Effect.
  11. Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis.
  12. Mesothelin Gene Variants Affect Soluble Mesothelin-Related Protein Levels in the Plasma of Asbestos-Exposed Males and Mesothelioma Patients from Germany.
  1. Diagnostics (Basel). 2022 Dec 01. pii: 3009. [Epub ahead of print]12(12):
    Diagnostic and Therapeutic Challenges of Malignant Pleural Mesothelioma.
    Jacopo Moro, Simona Sobrero, Carlotta Francesca Cartia, Simona Ceraolo, Roberta Rapanà, Federico Vaisitti, Stefano Ganio, Federica Mellone, Stefano Rudella, Federico Scopis, Danilo La Paglia, Carola Crystel Cacciatore, Enrico Ruffini, Francesco Leo.
      Malignant pleural mesothelioma is a rare cancer characterized by a very poor prognosis. Exposure to asbestos is the leading cause of malignant pleural mesothelioma. The preinvasive lesions, the mesothelial hyperplasia and its possible evolution are the focus of the majority of the studies aiming to identify the treatable phase of the disease. The role of BAP-1 and MTAP in the diagnosis of mesothelioma in situ and in the prognosis of malignant pleural mesothelioma is the main topic of recent studies. The management of preinvasive lesions in mesothelioma is still unclear and many aspects are the subject of debate. The diagnosis, the disease staging and the accurate, comprehensive assessment of patients are three key instants for an appropriate management of patients/the disease.
    Keywords:  atypical mesothelial hyperplasia; invasive diagnosis of malignant pleural mesothelioma; mesothelioma genetics; mesothelioma histopathology; mesothelioma immunohistochemistry; pleural mesothelial hyperplasia
    DOI:  https://doi.org/10.3390/diagnostics12123009
  2. J Pers Med. 2022 Dec 02. pii: 1993. [Epub ahead of print]12(12):
    AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma.
    Federica Zito Marino, Carminia Maria Della Corte, Vincenza Ciaramella, Stefania Erra, Andrea Ronchi, Alfonso Fiorelli, Giovanni Vicidomini, Mario Santini, Giosuè Scognamiglio, Floriana Morgillo, Fortunato Ciardiello, Renato Franco, Marina Accardo.
      Malignant pleural mesothelioma (MPM) is a highly lethal malignancy that unfortunately cannot benefit from molecularly targeted therapies. Although previous results showed the pivotal role of various receptor tyrosine kinases (RTKs) in MPM tumorigenesis, the treatment with a single inhibitor targeting one specific RTK has been shown to be ineffective in MPM patients. The main aim of the present study was to investigate the potential role of AXL and MET receptors in MPM and the possible efficacy of treatment with AXL and MET multitarget inhibitors. Immunohistochemical and FISH analyses were performed in a wide series of formalin-fixed paraffin-embedded MPM samples to detect the expression of two receptors and the potential gene amplification. In vitro studies were performed to evaluate putative correlations between the target's expression and the cell sensitivity to AXL-MET multitarget inhibitors. In our series, 10.4% of cases showed a co-expression of AXL and MET, regardless of their ligand expression, and the gene amplification. Furthermore, our in vitro results suggest that the concomitant pharmacological inhibition of AXL and MET may affect the proliferative and aggressiveness of MPM cells. In conclusion, the subset of MPM patients with AXL-MET co-activation could benefit from treatment with specific multitarget inhibitors.
    Keywords:  AXL; MET; malignant pleural mesothelioma (MPM); targeted tyrosine kinase inhibitor (TKIs)
    DOI:  https://doi.org/10.3390/jpm12121993
  3. Medicina (Kaunas). 2022 Dec 19. pii: 1874. [Epub ahead of print]58(12):
    Clinical, Laboratory, Histological, Radiological, and Metabolic Features and Prognosis of Malignant Pleural Mesothelioma.
    Yuan Zhang, Ran Li, Yumei Gu, Yuerong LiZhu, Xiaofang Liu, Shu Zhang.
      Background: Malignant pleural mesothelioma (MPM) is an aggressive and rare malignant pleural tumor. Methods: MPM patients diagnosed in Beijing Chaoyang Hospital and Beijing Tongren Hospital were the focus of this study. We collected and analyzed the histological, radiological, and metabolic features of MPM patients. At the same time, Cox univariable and multivariable analyses were used to explore the laboratory risk factors affecting the prognosis of MPM patients. Results: A total of 129 MPM patients were included in this study. MPM includes three main histological subtypes: epithelioid, sarcomatoid and biphasic. Among them, epithelial subtypes accounted for the highest proportion. Calretinin, Wilms' tumor gene (WT1), cytokeratin 5/6 (CK5/6), and D2-40 were the most useful mesothelial markers to support a MPM diagnosis. The imaging features of MPM patients are pleural thickening and pleural effusion. In PET-CT, the affected pleura showed obvious high uptake of tracer, and the degree was related to the specific subtype. The median follow-up time was 55.0 (30.0, 94.0) months. A total of 92 (71.3%) patients died during follow-up. The median survival time of patients was 21.0 (9.0, 48.0) months. The Cox multivariable analysis showed that age [hazard ratio (HR), 1.824; 95% confidence interval (CI) 1.159-2.872; p = 0.009; uncorrected], ESR (HR, 2.197; 95% CI 1.318-3.664; p = 0.003; with Bonferroni correction), lymphocytes (HR, 0.436; 95% CI 0.258-0.737; p = 0.002; with Bonferroni correction), platelets (HR, 1.802; 95% CI 1.084-2.997; p = 0.023; uncorrected) and total protein (HR, 0.625; 95% CI 0.394-0.990; p = 0.045; uncorrected) were independent risk factors for prognosis, after adjusting for confounding factors. Conclusions: Age, ESR, lymphocytes, platelets and total protein may be related to the prognosis of MPM patients. Summarizing the histological, radiological, and metabolic features of MPM patients in the two centers can increase clinicians' understanding of this rare tumor.
    Keywords:  PET-CT metabolic characteristics; histological features; malignant pleural mesothelioma; prognosis; radiological characteristics
    DOI:  https://doi.org/10.3390/medicina58121874
  4. J Thorac Oncol. 2022 Dec 19. pii: S1556-0864(22)01928-1. [Epub ahead of print]
    Considerations for Imaging of Malignant Pleural Mesothelioma: A Consensus Statement from the International Mesothelioma Interest Group (iMig).
    Sharyn I Katz, Christopher M Straus, Leonid Roshkovan, Kevin G Blyth, Thomas Frauenfelder, Ritu R Gill, Ferry Lalezari, Jeremy Erasmus, Anna K Nowak, Victor H Gerbaudo, Roslyn J Francis, Samuel G Armato.
      Malignant pleural mesothelioma (MPM) is an aggressive primary malignancy of the pleura that presents unique radiologic challenges with regards to accurate and reproducible assessment of disease extent at staging and follow-up imaging. By optimizing and harmonizing technical approaches to imaging MPM, the best quality imaging can be achieved for individual patient care, clinical trials and imaging research. This consensus statement represents agreement on harmonized, standard practices for routine multi-modality imaging of MPM, including radiography, computed tomography (CT), 18F-2-deoxy-D-glucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI), by an international panel of experts in the field of pleural imaging assembled by the International Mesothelioma Interest Group (iMig). In addition, modality-specific technical considerations and future directions are discussed. A bulleted summary of all technical recommendations is provided.
    Keywords:  computed tomography; guidelines; magnetic resonance imaging; malignant mesothelioma; positron-emission tomography; radiography
    DOI:  https://doi.org/10.1016/j.jtho.2022.11.018
  5. Diagnostics (Basel). 2022 Nov 22. pii: 2905. [Epub ahead of print]12(12):
    New Insights in Pleural Mesothelioma Classification Update: Diagnostic Traps and Prognostic Implications.
    Maria Giovanna Mastromarino, Alessandra Lenzini, Vittorio Aprile, Greta Alì, Diana Bacchin, Stylianos Korasidis, Marcello Carlo Ambrogi, Marco Lucchi.
      The 2021 WHO Classification of Tumors of the Pleura has introduced significant changes in mesothelioma codification beyond the three current histological subtypes-epithelioid, sarcomatoid and biphasic. Major advances since the 2015 WHO classification include nuclear grading and the introduction of architectural patterns, cytological and stromal features for epithelioid diffuse mesothelioma. Mesothelioma in situ has been recognized as a diagnostic category. Demonstration of loss of BAP1 or MTAP by immunohistochemistry, or CDKN2A homozygous deletion by FISH, is valuable in establishing the diagnosis of epithelioid mesothelioma. Recent emerging data proved that grading and histological subtypes have prognostic implications and may be helpful to patient risk stratification and clinical management. Nevertheless, the latest mesothelioma classification increases the already non-negligible diagnostic pitfalls, especially concerning differential diagnosis of pre-invasive tumors. In this review, recent changes in histologic classification of mesothelioma and advances in molecular markers are presented and their relation to diagnostic challenges and prognostic implications is discussed.
    Keywords:  epithelioid mesothelioma; histological subtypes; histology; malignant pleural mesothelioma; mesothelioma classification; mesothelioma diagnosis; tumor grade
    DOI:  https://doi.org/10.3390/diagnostics12122905
  6. Tuberk Toraks. 2022 Dec;70(4): 341-348
    The clinical utility of the LENT score in patients with malignant pleural mesothelioma.
    Yasemin Söyler, Suna Kavurgacı, Ezgi Gürel Akan, Ülkü Yılmaz.
       Introduction: In malignant pleural mesothelioma (MPM), useful tools are needed to predict survival. Thus, we aimed to evaluate the LENT score, and demonstrate the performance of the LENT score in predicting survival in patients with MPM.
    Materials and Methods: This was a retrospective, observational single-center study. Sixty-nine patients diagnosed with MPM who had pleural effusion (March 2009-December 2020) were divided into groups according to their LENT score and compared. Median survivals were estimated and compared according to the LENT score and parameters of the LENT score.
    Result: Fifty-four patients were in the low-LENT score group, 15 patients were in the moderate-LENT score group, and there were no patients in the highLENT score group. The two groups had similar characteristics in terms of age, gender, and histological subtype distribution. There were no patients with ECOG-PS 0 in the moderate-LENT score group. Serum neutrophil-tolymphocyte ratio (NLR), pleural lactate dehydrogenase (LDH), patients with serum NLR> 9, and patients with pleural LDH> 1500 were significantly higher in the moderate-LENT score group (p= 0.002, 0.001, <0.01, <0.01, respectively). Fifty patients had died during a median follow-up of 38.6 ± 6.5 (95% CI= 25.84-51.41) months. The median survival for all patients was 28.63 ± 3.2 (95% CI= 22.33-34.92) months, higher than the original study. It was 30.97 ± 2 months in the low-LENT score group, and 20.7 ± 3.4 months in the moderate-LENT score group (p= 0.98). The median survival for patients with pleural LDH<1500 was significantly higher than for patients with pleural LDH> 1500 (p= 0.006) (30.97 vs. 16.73 months), while ECOG-PS (0 vs. 1) and NLR (<9 vs. >9) showed no differences.
    Conclusions: The survival in our resultant groups was higher than those reported in the original study, and the LENT score had no discriminatory ability for predicting survival in patients with MPM. We nevertheless believe that before reaching more definite conclusions, further large-scale multicenter prospective studies are needed to better define the clinical utility of the LENT score.
    DOI:  https://doi.org/10.5578/tt.20229605
  7. Life (Basel). 2022 Nov 24. pii: 1969. [Epub ahead of print]12(12):
    Quantitative Assessment of Asbestos Fibers in Normal and Pathological Peritoneal Tissue-A Scoping Review.
    Yohama Caraballo-Arias, Carlotta Zunarelli, Paola Caffaro, Francesco Roccuzzo, Mattia Roberto Nocilla, Maria Chiara Imperiale, Clara Romano, Paolo Boffetta, Francesco Saverio Violante.
      Peritoneal tissue is the second most affected site by malignant mesothelioma linked to asbestos exposure. This scoping review aims to summarize the findings of the studies in which asbestos fibers in the peritoneum were quantified by electron microscopy, occasionally associated with spectroscopy, both in neoplastic and non-neoplastic tissue. The 9 studies selected comprised 62 cases, out of whom 100 samples were analyzed. Asbestos fibers were detected in 58 samples (58%). In addition, 28 cases had diagnosis of peritoneal mesothelioma. For 32 cases, a lung tumor sample was available: 28/32 samples analyzed presented asbestos fibers; 18/32 reported amphiboles with a range from not detected to 14.2 million fibers per gram of dry tissue (mfgdt); 18/32 reported chrysotile, with a range of 0 to 90 mfgdt. The studies were heterogeneous for type of samples, analytical technology, and circumstances of exposure to asbestos. To evaluate asbestos fibers in the peritoneum and to better understand the association between asbestos exposure and malignant peritoneal mesothelioma, it is desirable that the search for asbestos fibers becomes a routine process every time peritoneal tissue is accessible.
    Keywords:  amphiboles; asbestos fibers; chrysotile; electron microscopy; occupational diseases; peritoneal mesothelioma; scoping review
    DOI:  https://doi.org/10.3390/life12121969
  8. Curr Opin Anaesthesiol. 2023 Feb 01. 36(1): 74-82
    Presurgical radiation and chemotherapy in preparation for thoracic tumor resection.
    Iran Tavakoli, Simon R Turner, Ilitch Diaz-Gutierrez.
       PURPOSE OF REVIEW: This article aims at describing the role of neoadjuvant chemotherapy, radiation therapy as well the novel immunotherapy and targeted therapy in thoracic oncology with focus on anesthetic considerations of such treatments for the surgical patient.
    RECENT FINDINGS: In recent years, immune check point inhibitors have changed the landscape of thoracic oncology treatment. In this review, we summarize the key studies that have been fundamental in this change.
    SUMMARY: Rather than a comprehensive review, the purpose of this work is to provide the reader with an overview of the most common neoadjuvant regimens used in current practice, with the corresponding most prevalent adverse effects as it pertains for patients with esophageal and lung cancer, malignant pleural mesothelioma and mediastinal tumors. Considerations relevant to the anesthesiologist, including specific toxicities related to each treatment type, and the impact of each treatment type on perioperative outcomes and complications will be discussed.
    DOI:  https://doi.org/10.1097/ACO.0000000000001224
  9. Oncogene. 2022 Dec 22.
    BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms.
    Anita Singh, Sara Busacca, Aarti Gaba, Michael Sheaff, Charlotte Poile, Apostolos Nakas, Joanna Dzialo, Aleksandra Bzura, Alan G Dawson, Dean A Fennell, Andrew M Fry.
      The tumour suppressor BRCA1-associated protein 1 (BAP1) is the most frequently mutated cancer gene in mesothelioma. Here we report novel functions for BAP1 in mitotic progression highlighting the relationship between BAP1 and control of genome stability in mesothelioma cells with therapeutic implications. Depletion of BAP1 protein induced proteasome-mediated degradation of BRCA1 in mesothelioma cells while loss of BAP1 correlated with BRCA1 loss in mesothelioma patient tumour samples. BAP1 loss also led to mitotic defects that phenocopied the loss of BRCA1 including spindle assembly checkpoint failure, centrosome amplification and chromosome segregation errors. However, loss of BAP1 also led to additional mitotic changes that were not observed upon BRCA1 loss, including an increase in spindle length and enhanced growth of astral microtubules. Intriguingly, these consequences could be explained by loss of expression of the KIF18A and KIF18B kinesin motors that occurred upon depletion of BAP1 but not BRCA1, as spindle and astral microtubule defects were rescued by re-expression of KIF18A and KIF18B, respectively. We therefore propose that BAP1 inactivation causes mitotic defects through BRCA1-dependent and independent mechanisms revealing novel routes by which mesothelioma cells lacking BAP1 may acquire genome instability and exhibit altered responses to microtubule-targeted agents.
    DOI:  https://doi.org/10.1038/s41388-022-02577-3
  10. Cureus. 2022 Nov;14(11): e31579
    A Case Report of Mesothelioma Response to Endocrine Therapy in Synchronous Breast Cancer and Pleural Epithelioid Mesothelioma: A Double Exemestane Effect.
    Marta Pina, Rute Fernandes, Diogo Fonseca, Cristina Oliveira, Ana Rodrigues.
      Synchronous pleural mesothelioma (PM) and breast cancer are extremely rare. We present the case of a 53-year-old female diagnosed with localized breast cancer. She was radically treated with surgery, but during the adjuvant radiotherapy, the patient developed fever and dyspnoea, and pleural thickening was found on a CT scan. The biopsy confirmed the diagnosis of a synchronous malignancy - pleural epithelioid mesothelioma. The patient stopped radiotherapy and started adjuvant endocrine therapy with exemestane, a third-generation aromatase inhibitor, with an unexpected partial response to the PM. The patient remains on exemestane with a sustained partial response. This is a rare case of synchronous tumours that show a real-life benefit of exemestane in the treatment of pleural mesothelioma, which was only described in vitro, with a good sustained response. This suggests a potential for exemestane in the treatment of mesothelioma, which is an aggressive form of cancer with few therapeutics with sustained results.
    Keywords:  breast cancer; endocrine therapy; exemestane; pleural mesothelioma; synchronous tumours
    DOI:  https://doi.org/10.7759/cureus.31579
  11. Cancers (Basel). 2022 Dec 09. pii: 6063. [Epub ahead of print]14(24):
    Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis.
    Maria Gemelli, Diego Luigi Cortinovis, Alice Baggi, Pierluigi di Mauro, Stefano Calza, Alfredo Berruti, Salvatore Grisanti, Matteo Rota.
      Many clinical trials have investigated the role of ICIs in PM, with contrasting results. We performed a systematic review and meta-analysis of clinical trials testing single-agent anti-Programmed Death -1 (PD-1)/Programmed Death-Ligand 1 (PD-L1), anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or combined treatment in PM patients, analyzing response and survival rate as well as safety data. We selected 17 studies including 2328 patients. Both OS and PFS rates were significantly higher with combined ICI treatments than with single agent anti-PD-1/PD-L1 (p &lt; 0.001 and p = 0.006, respectively) or anti CTLA-4 (p &lt; 0.001) treatments. ORR and DCR for all ICI treatments were 20% (95% CI 13-27%) and 56% (95% CI 45-67%), respectively, and they did not significantly differ between combined and single agent treatments (p = 0.088 and p = 0.058, respectively). The 12-month OS and 6-month PFS rates did not differ significantly (p = 0.0545 and p = 0.1464, respectively) among pre-treated or untreated patients. Combined ICI treatments had a significantly higher rate of Adverse Events (AEs) (p = 0.01). PD-L1-positive patients had a higher probability of response and survival. In conclusion, combined ICI treatments have higher efficacy than single agents but are limited by higher toxicity. Efficacy was independent of treatment line, so a customized sequential strategy should still be speculated. PD-L1 expression could influence response to ICIs; however, reliable biomarkers are warranted.
    Keywords:  anti CTLA-4; anti PD-1/PD-L1; immune checkpoint inhibitors; immunotherapy; pleural mesothelioma
    DOI:  https://doi.org/10.3390/cancers14246063
  12. Biology (Basel). 2022 Dec 14. pii: 1826. [Epub ahead of print]11(12):
    Mesothelin Gene Variants Affect Soluble Mesothelin-Related Protein Levels in the Plasma of Asbestos-Exposed Males and Mesothelioma Patients from Germany.
    MoMar Study Group
      Malignant mesothelioma (MM) is a severe disease mostly caused by asbestos exposure. Today, one of the best available biomarkers is the soluble mesothelin-related protein (SMRP), also known as mesothelin. Recent studies have shown that mesothelin levels are influenced by individual genetic variability. This study aimed to investigate the influence of three mesothelin (MSLN) gene variants (SNPs) in the 5'-untranslated promoter region (5'-UTR), MSLN rs2235503 C &gt; A, rs3764246 A &gt; G, rs3764247 A &gt; C, and one (rs1057147 G &gt; A) in the 3'-untranslated region (3'-UTR) of the MSLN gene on plasma concentrations of mesothelin in 410 asbestos-exposed males without cancer and 43 males with prediagnostic MM (i.e., with MM diagnosed later on) from the prospective MoMar study, as well as 59 males with manifest MM from Germany. The mesothelin concentration differed significantly between the different groups (p &lt; 0.0001), but not between the prediagnostic and manifest MM groups (p = 0.502). Five to eight mutations of the four SNP variants studied were associated with increased mesothelin concentrations (p = 0.001). The highest mesothelin concentrations were observed for homozygous variants of the three promotor SNPs in the 5'-UTR (p &lt; 0.001), and the highest odds ratio for an elevated mesothelin concentration was observed for MSLN rs2235503 C &gt; A. The four studied SNPs had a clear influence on the mesothelin concentration in plasma. Hence, the analysis of these SNPs may help to elucidate the diagnostic background of patients displaying increased mesothelin levels and might help to reduce false-positive results when using mesothelin for MM screening in high-risk groups.
    Keywords:  MoMar cohort; asbestos; biomarker; blood test; confounder; manifest mesothelioma; mesothelin; prediagnostic mesothelioma; prospective study; variant
    DOI:  https://doi.org/10.3390/biology11121826
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